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Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: Bladder cancer (BCa) is a highly heterogeneous malignancy, and precision treatment remains challenging. Identifying molecular biomarkers and risk factors is essential for improving prognosis and therapeutic strategies. Methods: We integrated expression quantitative trait loci (eQTL) data with Mendelian randomization (MR) analysis to identify candidate risk genes associated with BCa. Subsequently, a prognostic risk model was developed using machine learning methods to explore its correlation with molecular features, immune cell infiltration, and ferroptosis-related pathways. Based on these findings, the Tripartite Motif Containing 59 (TRIM59) protein was selected for further experimental validation. The functional role of TRIM59 in BCa progression was further investigated using MTT assays in BCa cell lines. Additionally, western blotting (WB) was conducted to confirm the potential association between TRIM59 expression and ferroptosis regulation. Results: The risk model identified distinct signaling pathways that differentiate the high-risk and low-risk BCa groups. The low-risk group demonstrated greater infiltration of CD8+ T cells. Conversely, the high-risk group exhibited enhanced immune evasion, as evidenced by increased infiltration of macrophages and fibroblasts. Furthermore, TRIM59 exerts a regulatory influence on ferroptosis progression in BCa by modulating key genes involved in this process, including Solute Carrier Family 7 Member 11 (SLC7A11), Glutathione Peroxidase 4 (GPX4), and Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4). Conclusion: Our integrative approach highlights the potential of genomic and immune microenvironment data in developing personalized risk models for BCa, offering insights into individualized treatment strategies. Importantly, TRIM59 is involved in ferroptosis resistance in BCa. These findings have potential implications for identifying diagnostic biomarkers and therapeutic targets for BCa treatment.<\/jats:p>","DOI":"10.31083\/fbl44395","type":"journal-article","created":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T04:43:39Z","timestamp":1760157819000},"source":"Crossref","is-referenced-by-count":4,"title":["Identification of TRIM59 as a Key Biomarker for Ferroptosis Resistance and Immunotherapy Response in Bladder Cancer via Multi-Omics Integration and Machine Learning"],"prefix":"10.31083","volume":"30","author":[{"given":"Jianyuan","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Pathology, Shaanxi Provincial People\u2019s Hospital, 710068 Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathology, Shaanxi Provincial People\u2019s Hospital, 710068 Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanchun","family":"Qu","sequence":"first","affiliation":[{"name":"Department of Pathology, The Second Hospital of Tianjin Medical University, 300211 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingfen","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathology, The Second Hospital of Tianjin Medical University, 300211 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianglian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pathology, The Second Hospital of Tianjin Medical University, 300211 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"first","affiliation":[{"name":"Department of Blood Transfusion, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1603-637X","authenticated-orcid":true,"given":"Pengyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Blood Transfusion, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: a Cancer Journal for Clinicians. 2021; 71: 209\u2013249.","DOI":"10.3322\/caac.21660"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Liu S, Chen X, Lin T. Emerging strategies for the improvement of chemotherapy in bladder cancer: Current knowledge and future perspectives. Journal of Advanced Research. 2022; 39: 187\u2013202.","DOI":"10.1016\/j.jare.2021.11.010"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Flaig TW, Spiess PE, Agarwal N, Bangs R, Boorjian SA, Buyyounouski MK, et al. NCCN Guidelines Insights: Bladder Cancer, Version 5.2018. Journal of the National Comprehensive Cancer Network. 2018; 16: 1041\u20131053.","DOI":"10.6004\/jnccn.2018.0072"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Lenis AT, Lec PM, Chamie K, Mshs MD. Bladder Cancer: A Review. JAMA. 2020; 324: 1980\u20131991.","DOI":"10.1001\/jama.2020.17598"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Tran L, Xiao JF, Agarwal N, Duex JE, Theodorescu D. Advances in bladder cancer biology and therapy. Nature Reviews. Cancer. 2021; 21: 104\u2013121.","DOI":"10.1038\/s41568-020-00313-1"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Cathomas R, Lorch A, Bruins HM, Comp\u00e9rat EM, Cowan NC, Efstathiou JA, et al. The 2021 Updated European Association of Urology Guidelines on Metastatic Urothelial Carcinoma. European Urology. 2022; 81: 95\u2013103.","DOI":"10.1016\/j.eururo.2021.09.026"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Leyderman M, Chandrasekar T, Grivas P, Li R, Bhat S, Basnet A, et al. Metastasis development in non-muscle-invasive bladder cancer. Nature Reviews. Urology. 2025; 22: 375\u2013386.","DOI":"10.1038\/s41585-024-00963-y"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Lopez-Beltran A, Cookson MS, Guercio BJ, Cheng L. Advances in diagnosis and treatment of bladder cancer. BMJ (Clinical Research Ed.). 2024; 384: e076743.","DOI":"10.1136\/bmj-2023-076743"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Katoh M, Loriot Y, Brandi G, Tavolari S, Wainberg ZA, Katoh M. FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions. Nature Reviews. Clinical Oncology. 2024; 21: 312\u2013329.","DOI":"10.1038\/s41571-024-00869-z"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Picard LC, Rich FJ, Kenwright DN, Stevens AJ. Epigenetic changes associated with Bacillus Calmette-Guerin (BCG) treatment in bladder cancer. Biochimica et Biophysica Acta. Reviews on Cancer. 2024; 1879: 189123.","DOI":"10.1016\/j.bbcan.2024.189123"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Liu Q, Guan Y, Li S. Programmed death receptor (PD-)1\/PD-ligand (L)1 in urological cancers: the \u201call-around warrior\u201d in immunotherapy. Molecular Cancer. 2024; 23: 183.","DOI":"10.1186\/s12943-024-02095-8"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Nadal R, Valderrama BP, Bellmunt J. Progress in systemic therapy for advanced-stage urothelial carcinoma. Nature Reviews. Clinical Oncology. 2024; 21: 8\u201327.","DOI":"10.1038\/s41571-023-00826-2"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Choi W, Porten S, Kim S, Willis D, Plimack ER, Hoffman-Censits J, et al. Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell. 2014; 25: 152\u2013165.","DOI":"10.1016\/j.ccr.2014.01.009"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Damrauer JS, Hoadley KA, Chism DD, Fan C, Tiganelli CJ, Wobker SE, et al. Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology. Proceedings of the National Academy of Sciences of the United States of America. 2014; 111: 3110\u20133115.","DOI":"10.1073\/pnas.1318376111"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Mo Q, Nikolos F, Chen F, Tramel Z, Lee YC, Hayashi K, et al. Prognostic Power of a Tumor Differentiation Gene Signature for Bladder Urothelial Carcinomas. Journal of the National Cancer Institute. 2018; 110: 448\u2013459.","DOI":"10.1093\/jnci\/djx243"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Rebouissou S, Bernard-Pierrot I, de Reyni\u00e8s A, Lepage ML, Krucker C, Chapeaublanc E, et al. EGFR as a potential therapeutic target for a subset of muscle-invasive bladder cancers presenting a basal-like phenotype. Science Translational Medicine. 2014; 6: 244ra91.","DOI":"10.1126\/scitranslmed.3008970"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Robertson AG, Kim J, Al-Ahmadie H, Bellmunt J, Guo G, Cherniack AD, et al. Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer. Cell. 2018; 174: 1033.","DOI":"10.1016\/j.cell.2018.07.036"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Sj\u00f6dahl G, Lauss M, L\u00f6vgren K, Chebil G, Gudjonsson S, Veerla S, et al. A molecular taxonomy for urothelial carcinoma. Clinical Cancer Research. 2012; 18: 3377\u20133386.","DOI":"10.1158\/1078-0432.CCR-12-0077-T"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Kamoun A, de Reyni\u00e8s A, Allory Y, Sj\u00f6dahl G, Robertson AG, Seiler R, et al. A Consensus Molecular Classification of Muscle-invasive Bladder Cancer. European Urology. 2020; 77: 420\u2013433.","DOI":"10.1016\/j.eururo.2019.09.006"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Jia Q, Wu W, Wang Y, Alexander PB, Sun C, Gong Z, et al. Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer. Nature Communications. 2018; 9: 5361.","DOI":"10.1038\/s41467-018-07767-w"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Jiang P, Gu S, Pan D, Fu J, Sahu A, Hu X, et al. Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response. Nature Medicine. 2018; 24: 1550\u20131558.","DOI":"10.1038\/s41591-018-0136-1"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Geeleher P, Cox N, Huang RS. pRRophetic: an R package for prediction of clinical chemotherapeutic response from tumor gene expression levels. PLoS ONE. 2014; 9: e107468.","DOI":"10.1371\/journal.pone.0107468"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Carrot-Zhang J, Chambwe N, Damrauer JS, Knijnenburg TA, Robertson AG, Yau C, et al. Comprehensive Analysis of Genetic Ancestry and Its Molecular Correlates in Cancer. Cancer Cell. 2020; 37: 639\u2013654.","DOI":"10.1016\/j.ccell.2020.04.012"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Lv J, Song Q, Bai K, Han J, Yu H, Li K, et al. N6-methyladenosine-related single-nucleotide polymorphism analyses identify oncogene RNFT2 in bladder cancer. Cancer Cell International. 2022; 22: 301.","DOI":"10.1186\/s12935-022-02701-z"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Ma L, Zhang D, Huang Z, Zheng R, Du M, Lv Q, et al. Functional variants of RPS6KB1 and PIK3R1 in the autophagy pathway genes and risk of bladder cancer. Archives of Toxicology. 2022; 96: 367\u2013375.","DOI":"10.1007\/s00204-021-03173-2"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Lin Y, Ge Y, Wang Y, Ma G, Wang X, Liu H, et al. The association of rs710886 in lncRNA PCAT1 with bladder cancer risk in a Chinese population. Gene. 2017; 627: 226\u2013232.","DOI":"10.1016\/j.gene.2017.06.021"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Li H, Achour I, Bastarache L, Berghout J, Gardeux V, Li J, et al. Integrative genomics analyses unveil downstream biological effectors of disease-specific polymorphisms buried in intergenic regions. NPJ Genomic Medicine. 2016; 1: 16006.","DOI":"10.1038\/npjgenmed.2016.6"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Lim YW, Chen-Harris H, Mayba O, Lianoglou S, Wuster A, Bhangale T, et al. Germline genetic polymorphisms influence tumor gene expression and immune cell infiltration. Proceedings of the National Academy of Sciences of the United States of America. 2018; 115: E11701\u2013E11710.","DOI":"10.1073\/pnas.1804506115"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Pineda S, Van Steen K, Malats N. Integrative eQTL analysis of tumor and host omics data in individuals with bladder cancer. Genetic Epidemiology. 2017; 41: 567\u2013573.","DOI":"10.1002\/gepi.22053"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Qian WJ, Yan JS, Gang XY, Xu L, Shi S, Li X, et al. Intercellular adhesion molecule-1 (ICAM-1): From molecular functions to clinical applications in cancer investigation. Biochimica et Biophysica Acta. Reviews on Cancer. 2024; 1879: 189187.","DOI":"10.1016\/j.bbcan.2024.189187"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Yan J, Zhuang L, Wang Y, Jiang Y, Tu Z, Dong C, et al. Inhibitors of cell cycle checkpoint target Wee1 kinase - a patent review (2003-2022). Expert Opinion on Therapeutic Patents. 2022; 32: 1217\u20131244.","DOI":"10.1080\/13543776.2022.2166827"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Hidalgo I, Sorolla MA, Sorolla A, Salud A, Parisi E. Secreted Phospholipases A2: Drivers of Inflammation and Cancer. International Journal of Molecular Sciences. 2024; 25: 12408.","DOI":"10.3390\/ijms252212408"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Moon H, White AC, Borowsky AD. New insights into the functions of Cox-2 in skin and esophageal malignancies. Experimental & Molecular Medicine. 2020; 52: 538\u2013547.","DOI":"10.1038\/s12276-020-0412-2"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Wan M, Tang X, Stsiapanava A, Haeggstr\u00f6m JZ. Biosynthesis of leukotriene B4. Seminars in Immunology. 2017; 33: 3\u201315.","DOI":"10.1016\/j.smim.2017.07.012"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Lu W, Aihaiti A, Abudukeranmu P, Liu Y, Gao H. Arachidonic acid metabolism as a novel pathogenic factor in gastrointestinal cancers. Molecular and Cellular Biochemistry. 2025; 480: 1225\u20131239.","DOI":"10.1007\/s11010-024-05057-2"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Goto T, Miyamoto H. The Role of Estrogen Receptors in Urothelial Cancer. Frontiers in Endocrinology. 2021; 12: 643870.","DOI":"10.3389\/fendo.2021.643870"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Pereira F, Domingues MR, Vitorino R, Guerra IMS, Santos LL, Ferreira JA, et al. Unmasking the Metabolite Signature of Bladder Cancer: A Systematic Review. International Journal of Molecular Sciences. 2024; 25: 3347.","DOI":"10.3390\/ijms25063347"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Iacovino ML, Miceli CC, De Felice M, Barone B, Pompella L, Chiancone F, et al. Novel Therapeutic Opportunities in Neoadjuvant Setting in Urothelial Cancers: A New Horizon Opened by Molecular Classification and Immune Checkpoint Inhibitors. International Journal of Molecular Sciences. 2022; 23: 1133.","DOI":"10.3390\/ijms23031133"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"DeNardo DG, Ruffell B. Macrophages as regulators of tumour immunity and immunotherapy. Nature Reviews. Immunology. 2019; 19: 369\u2013382.","DOI":"10.1038\/s41577-019-0127-6"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Koll FJ, Banek S, Kluth L, K\u00f6llermann J, Bankov K, Chun FKH, et al. Tumor-associated macrophages and Tregs influence and represent immune cell infiltration of muscle-invasive bladder cancer and predict prognosis. Journal of Translational Medicine. 2023; 21: 124.","DOI":"10.1186\/s12967-023-03949-3"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Mariathasan S, Turley SJ, Nickles D, Castiglioni A, Yuen K, Wang Y, et al. TGF\u03b2 attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018; 554: 544\u2013548.","DOI":"10.1038\/nature25501"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"van Dorp J, van der Heijden MS. The bladder cancer immune micro-environment in the context of response to immune checkpoint inhibition. Frontiers in Immunology. 2023; 14: 1235884.","DOI":"10.3389\/fimmu.2023.1235884"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Wang J, Lu Q, Chen X, Aifantis I. Targeting MHC-I inhibitory pathways for cancer immunotherapy. Trends in immunology, 2024; 45, 177\u2013187.","DOI":"10.1016\/j.it.2024.01.009"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Rizvi H, Sanchez-Vega F, La K, Chatila W, Jonsson P, Halpenny D, et al. Molecular Determinants of Response to Anti-Programmed Cell Death (PD)-1 and Anti-Programmed Death-Ligand 1 (PD-L1) Blockade in Patients With Non-Small-Cell Lung Cancer Profiled With Targeted Next-Generation Sequencing. Journal of Clinical Oncology. 2018; 36: 633\u2013641.","DOI":"10.1200\/JCO.2017.75.3384"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease. Nature Reviews. Molecular Cell Biology. 2021; 22: 266\u2013282.","DOI":"10.1038\/s41580-020-00324-8"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Wang Y, Wu N, Li J, Liang J, Zhou D, Cao Q, et al. The interplay between autophagy and ferroptosis presents a novel conceptual therapeutic framework for neuroendocrine prostate cancer. Pharmacological Research. 2024; 203: 107162.","DOI":"10.1016\/j.phrs.2024.107162"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Shen L, Zhang J, Zheng Z, Yang F, Liu S, Wu Y, et al. PHGDH Inhibits Ferroptosis and Promotes Malignant Progression by Upregulating SLC7A11 in Bladder Cancer. International Journal of Biological Sciences. 2022; 18: 5459\u20135474.","DOI":"10.7150\/ijbs.74546"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Lv T, Fan X, He C, Zhu S, Xiong X, Yan W, et al. SLC7A11-ROS\/\u03b1KG-AMPK axis regulates liver inflammation through mitophagy and impairs liver fibrosis and NASH progression. Redox Biology. 2024; 72: 103159.","DOI":"10.1016\/j.redox.2024.103159"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"Jiang Y, Sun M. SLC7A11: the Achilles heel of tumor? Frontiers in Immunology. 2024; 15: 1438807.","DOI":"10.3389\/fimmu.2024.1438807"}],"container-title":["Frontiers in Bioscience-Landmark"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/30\/9\/10.31083\/FBL44395","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T04:45:04Z","timestamp":1760157904000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/30\/9\/10.31083\/FBL44395"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,29]]},"references-count":49,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025]]}},"alternative-id":["S2768-6701(25)01854-4"],"URL":"https:\/\/doi.org\/10.31083\/fbl44395","relation":{},"ISSN":["2768-6701","2768-6698"],"issn-type":[{"value":"2768-6701","type":"print"},{"value":"2768-6698","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,29]]},"article-number":"44395"}}